rs4887379

Positions:

• chr15-88184105-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001012338.3(NTRK3):​c.323+120G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 959,686 control chromosomes in the GnomAD database, including 22,800 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4532 hom., cov: 32)
  • Exomes 𝑓: 0.21 (18268 hom.)
• Consequence: NTRK3 NM_001012338.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.165

Genes affected

NTRK3 (HGNC:8033): (neurotrophic receptor tyrosine kinase 3) This gene encodes a member of the neurotrophic tyrosine receptor kinase (NTRK) family. This kinase is a membrane-bound receptor that, upon neurotrophin binding, phosphorylates itself and members of the MAPK pathway. Signalling through this kinase leads to cell differentiation and may play a role in the development of proprioceptive neurons that sense body position. Mutations in this gene have been associated with medulloblastomas, secretory breast carcinomas and other cancers. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2011]

NTRK3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 15-88184105-C-G is Benign according to our data. Variant chr15-88184105-C-G is described in ClinVar as [Benign]. Clinvar id is 1282760.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTRK3	NM_001012338.3	c.323+120G>C		intron_variant		ENST00000629765.3	NP_001012338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTRK3	ENST00000629765.3	c.323+120G>C		intron_variant		1	NM_001012338.3	ENSP00000485864.1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35891 AN: 151978 Hom.: 4528 Cov.: 32

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.235

GnomAD4 exome AF: 0.207 AC: 167279 AN: 807592 Hom.: 18268 AF XY: 0.210 AC XY: 88472 AN XY: 421046

Gnomad4 AFR exome AF: 0.306

Gnomad4 AMR exome AF: 0.254

Gnomad4 ASJ exome AF: 0.194

Gnomad4 EAS exome AF: 0.158

Gnomad4 SAS exome AF: 0.282

Gnomad4 FIN exome AF: 0.140

Gnomad4 NFE exome AF: 0.200

Gnomad4 OTH exome AF: 0.216

GnomAD4 genome AF: 0.236 AC: 35919 AN: 152094 Hom.: 4532 Cov.: 32 AF XY: 0.234 AC XY: 17382 AN XY: 74356

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.237

Alfa AF: 0.210 Hom.: 410

Bravo AF: 0.245

Asia WGS AF: 0.253 AC: 881 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4887379; hg19: chr15-88727336;